Long-latency modulation of motor cortex excitability by ipsilateral posterior inferior frontal gyrus and pre-supplementary motor area

Abstract

The primary motor cortex (M1) is strongly influenced by several frontal regions. Dual-site transcranial magnetic stimulation (dsTMS) has highlighted the timing of early (<40 ms) prefrontal/premotor influences over M1. Here we used dsTMS to investigate, for the first time, longer-latency causal interactions of the posterior inferior frontal gyrus (pIFG) and pre-supplementary motor area (pre-SMA) with M1 at rest. A suprathreshold test stimulus (TS) was applied over M1 producing a motor-evoked potential (MEP) in the relaxed hand. Either a subthreshold or a suprathreshold conditioning stimulus (CS) was administered over ipsilateral pIFG/pre-SMA sites before the TS at different CS-TS inter-stimulus intervals (ISIs: 40–150 ms). Independently of intensity, CS over pIFG and pre-SMA (but not over a control site) inhibited MEPs at an ISI of 40 ms. The CS over pIFG produced a second peak of inhibition at an ISI of 150 ms. Additionally, facilitatory modulations were found at an ISI of 60 ms, with supra- but not subthreshold CS intensities. These findings suggest differential modulatory roles of pIFG and pre-SMA in M1 excitability. In particular, the pIFG –but not the pre-SMA– exerts intensity-dependent modulatory influences over M1 within the explored time window of 40-150 ms, evidencing fine-tuned control of M1 output.

Long-latency interhemispheric interactions between motor-related areas and the primary motor cortex: a dual site TMS study

“…To localize the stimulation sites, we used established functional, craniometric and stereotaxic procedures. Each target site was identified on the scalp based on the most established procedure (e.g., functional methods for M1), and then the position of the coil was verified using a neuronavigation system 18 . Both the lM1 and the rM1 scalp sites were localized using functional procedures, i.e., by identifying the FDI motor hotspot.…”

“…The rPMv scalp site was identified using a neuronavigation system 18 , 48 – 50 . We used the SofTaxic Navigator system (EMS; Electro Medical Systems, Bologna, Italy), as in previous studies 18 , 51 – 55 . This system automatically estimates Talairach coordinates from a magnetic resonance imaging (MRI)-constructed stereotaxic template.…”

“…In a third, recent study by Fiori et al . 18 , our group also tested long-latency interactions between a rostral medial premotor site and lM1. Although we found site-specific effects of medial premotor subthreshold and suprathreshold conditioning over M1, our study did not focus on interhemispheric interactions, and thus did not include rM1 as a control CS site.…”

“…Therefore, an important and yet unanswered question is to what extent distinct ventral, dorsal and medial sectors of the premotor cortex in one hemisphere exert site-specific modulatory effects over the contralateral M1 resulting in a long-latency influence that is distinct from the influence exerted by M1 over its contralateral homologue. Disclosing site-specific premotor-motor interactions requires a systematic investigation of the effect of the CS location, but also CS intensity, as different TMS intensities can recruit partially distinct neural populations 18 , 38 .…”

“… 21 and Fiori et al . 18 , we focused on the influence that a CS over right hemispheric motor areas exerts over the contralateral M1. Therefore, the TS was administered over lM1, and MEPs were recorded from the right hand.…”